9. | Principles of Surgery, Companion Handbook

Chapter 8 Wound Care and Wound Healing

Principles of Surgery Companion Handbook

CHAPTER

8
WOUND CARE AND WOUND HEALING

General Considerations
	Classification of Wounds
	Types of Wound Closure
	Mechanisms Involved in Wound Healing
	Phases of Healing
	Cytokines in Wound Healing
	Extracellular Matrix Metabolism
	Wound Contraction
	Epithelialization
	Nutrition
	Immunosuppression
	Genetic Disorders of Connective Tissue
Specific Wound-Healing Problems
	Gastrointestinal Tract
	Skin
	Tendon
	Bone
	Cartilage
	Chronic Wounds
	Chronic Wound Care
Wound Dressings
Mechanical Wound Closure
Fetal Wound Healing

GENERAL CONSIDERATIONS

Classification of Wounds

Wounds are classified into two general categories: acute and chronic. Acute wounds repair through an orderly process that results in anatomic and functional integrity. By contrast, chronic wounds have failed to proceed through the orderly and timely process or have proceeded through a repair process without establishing an anatomic or functional result.

Types of Wound Closure

Primary closure approximates the acutely disrupted tissue with sutures, staples, or tape. With time, the synthesis, deposition, and cross-linking of collagen and other proteins provide the tissue with strength and integrity.

In delayed primary closure, approximation of the wound is delayed for several days after the wound has been created. This is indicated to prevent infection in wounds in which there has been a significant bacterial contamination, foreign bodies, or extensive tissue trauma.

Spontaneous closure, or secondary wound closure, occurs when the margins of the open wound move together by a biologic process of contraction. Partial-thickness wounds heal by the process of epithelialization that occurs first by migration and the mitosis of epithelial cells.

Mechanisms Involved in Wound Healing

Three distinct biologic mechanisms are involved in all healing processes. They include epithelialization, which is the process by which keratinocytes migrate and divide to resurface the skin or mucosa. Contraction is the mechanism whereby there is spontaneous closure of full-thickness skin wounds or constriction of tubular organs. Connective tissue matrix deposition is the process whereby fibroblasts are recruited to the site of injury and produce a new connective tissue matrix.

Phases of Healing

Under normal conditions, the phases of healing are divided into four specific events that actually overlap and have complex interactions. There is not a “lag phase” in the healing process.

Coagulation Injury causes hemorrhage and damage from blood vessels and lymphatics. Vasoconstriction occurs almost immediately. Vasoactive compounds initiate the process of diapedesis, the passage of intravascular cells through the vessel walls into the extravascular space of the wound. Platelets derived from the hemorrhage form a hemostatic clot and release clotting factors to produce fibrin, which is hemostatic. Fibrin forms a mesh for further migration of inflammatory cells in fibroblasts. Platelets also produce essential cytokines that modulate the events of wound healing.

Inflammation The inflammatory phase is characterized by the sequential migration of leukocytes into the wound. Inflammatory cells regulate the connective tissue matrix by specific messengers.

Fibroplasia During this phase, fibrous protein collagen is synthesized and cross-linked, and there is deposition of collagen and other matrix proteins that provide the healed wound with strength and integrity. Within 10 h after injury, there is evidence of increased wound collagen synthesis. After 5–7 days, collagen synthesis peaks and then declines gradually.

Remodeling During this phase, acute and chronic inflammatory cells diminish, angiogenesis ceases, and fibroplasia ends. The equilibrium between collagen synthesis and degradation is restored. The complex interactions of various processes during normal dermal wound healing are shown in Figure 8-1.

FIGURE 8-1 Sequence of events in wound healing. (Modified from: Mast BA: The Skin, in Cohen IK, Diegelmann RF, Lindblad WJ (eds): Wound Healing: Biochemical and Clinical Aspects, chap 22. Philadelphia, WB Saunders, 1992, with permission.)

Cytokines in Wound Healing

Cytokines are “wound hormones.” They may be endocrine, like somatomedin or insulin-like growth factor and circulate in the bloodstream to a distant target cell. Others are paracrine, produced by one cell and affecting an adjacent target cell. Examples of this are transforming growth factor beta (TGF-b) and platelet-derived growth factor (PDGF). Autocrine factors are secreted by a cell and then act on a receptor in the same cell. Finally, intracrine factors are produced by a cell and remain active in the same cell. Cytokines regulate cell proliferation and are also chemotactic, stimulating cells to migrate to the wound site. In addition, they direct the cells to produce specific components needed for matrix repair, including proteins, enzymes, proteoglycans, and attachment glycoproteins.

Extracellular Matrix Metabolism

The extracellular matrix has a number of cell types and components that interact with one another. Collagen is the major component of the extracellular matrix of all soft tissues, tendons, ligaments, and bones.

Synthesis Collagen is composed of three polypeptide chains, and each chain is formed in an orderly sequence. A key step in the formation is hydroxylation that requires hydroxyproline and cosubstrates. A lack of ascorbic acid or oxygen will compromise collagen production and result in insufficient wound strength. Collagen cross-linking occurs to form fibrils and fibers of collagen. The enzyme responsible for this step may be inhibited by b-aminopropionitrile (BAPN) and D-penicillamine.

Degradation For normal wound healing, collagen must be degraded as well as produced. This is initiated by metalloproteinases synthesized by inflammatory cells, fibroblasts, and epithelial cells.

Ground Substance This is made up of proteoglycans and glycosaminoglycans that occupy a significant amount of space in the extracellular matrix. They function as “shock absorbers.”

Wound Contraction

Contraction is one of the most powerful mechanical forces in the body. Contraction may result in a contracture that is a fixed deformity and often a functional disability. All attempts to use pharmacologic agents to control contraction of wounds have failed. Splinting a wound open will not prevent contracture. In an attempt to surgically correct contractures, plastic surgical procedures can result in recurrent contractures. Often it is preferable to correct the defect by placing a flap that contains both skin and subcutaneous tissue. In correcting a mature contracture, a skin graft may be used to fill the defect.

Epithelialization

While the collagen-rich dermis provides the strength attributed to skin, the epidermis provides the barrier that protects the host from the external environment. Partial-thickness wounds heal by the process of epithelialization. It incorporates both migration and mitosis. Migration is initiated in the deeper hair follicles and the sweat glands. The blood and tissue fluids contain fibronectin and vitronectin that support epithelial migration. Several growth factors stimulate keratinocyte migration and mitosis.

Nutrition

If caloric protein intake stops for 24 h, collagen synthesis ceases. Inadequate nutrition inhibits the immune response, and opsonization of bacteria is ineffective. The lack of ascorbic acid is the most common cause of wound-healing deficiency. Ascorbate is necessary for the metabolism and synthesis of collagen. In a scorbutic patient, scar tissue breaks down before there is healing of the normal skin.

Trace amounts of iron are needed for prolyl hydroxylation. Calcium and magnesium are required for collagenase activity and protein synthesis. All the essential amino acids are needed for wound healing. An adequate supply of oxygen is needed for wound healing.

Immunosuppression

Only a small number of immunosuppressed patients manifest clinical wound-healing problems. A direct relationship between a leukocyte defect and healing has not been reported. The wound complications found in acquired immune deficiency syndrome (AIDS) patients have not been defined. Chemotherapeutic anticancer drugs inhibit wound healing.

Genetic Disorders of Connective Tissue

Osteogenesis Imperfecta This is a congenital form of osteopenia due to mutations in the genes for Type I collagen. There is an increased propensity for bones to break under minimal stress. There is also dermal thinning and increased bruisability. Patients also have difficulty with excessive diaphoresis. Children with osteogenesis imperfecta have a higher incidence of hernias, but these can be corrected successfully by operation.

Ehlers-Danlos Syndrome This is characterized by joint laxity, skin hyperextensibility and fragility, poor wound healing, and vascular rupture. Due to connective tissue weakness, adolescent males are at an increased risk during their normal growth development. Adolescent females are at higher risk during the hormonal changes of menstruation. A number of vascular complications include arteriovenous fistulas, varicose veins, arterial rupture, and true and false aneurysms.

Marfan's Syndrome This is characterized by tall stature, arachnodactyly, lax ligaments, myopia, scoliosis, pectus excavatum, and often dissecting aneurysms of the root and ascending portions of the aorta. Wound healing is more complicated in these patients.

Epidermolysis Bullosa This is characterized by blistering and ulcerations. It is thought to be due to excessive production of matrix metalloproteinases by fibroblasts. Most of these ulcers heal spontaneously, but in the more severe forms the epithelium does not regenerate adequately, and inflammation and scarring ensue. Dermal incisions and tissue injury must have meticulous care to limit the amount of blistering in these patients. Phenytoin decreases collagenase activity and has been used to treat patients.

A number of factors may alter wound healing. They are listed in Table 8-1.

TABLE 8-1 FACTORS THAT AFFECT HEALING IN SURGICAL PRACTICE

SPECIFIC WOUND-HEALING PROBLEMS

Gastrointestinal Tract

Anatomy The inner mucosal layer is for absorption, and the outer muscularis mucosae layer is for motility. These are wrapped in a strong serosal layer, which is an extension of the peritoneum. Unlike the skin, the mucosal epithelium is only one cell thick and renews itself about every 8 days. The submucosa separates the mucosa from the muscularis propria and is composed of several collagen types. The muscularis propria is densely packed smooth muscle.

Injury and Repair The process is determined by the depth of injury and the chronicity of the injury. If the epithelium is injured, a rapid restitution process is initiated, and the epithelial lining is restored within hours. When the injury penetrates into the submucosa, an ulcer results. If the process is acute, the collagen laid down is resorbed, and the normal architecture of the intestine is preserved. If the process is chronic, scar tissue accumulates, and stricture may occur.

Crohn's disease is characterized by inflammation in the submucosa rather than the mucosa and often extends from the mucosa to the serosa (transmural). Inflammation leads to collagen deposition and contraction, which cause stricture. In ulcerative colitis, the inflammation is confined to the mucosa and does not extend into the submucosa. Radiation injury involves the submucosa, muscularis, and serosa with fibrosis and hyalinization of the accumulated collagen.

Healing in the Gastrointestinal Tract The same basic process of repair occurs with anastomotic healing in the gastrointestinal tract as occurs in skin. During the first few days after anastomosis, there is significant turnover of collagen at the anastomotic site and in the adjacent bowel wall.

Skin

Keloids and Hypertrophic Scars These are both abnormal healing processes that occur after injury. Hypertrophic scars remain within the boundaries of the original wound and almost always regress over a period of time. By contrast, keloids extend beyond the boundaries of the original wound and usually do not regress. They usually recur after excision unless additional therapy is provided. The rate of collagen synthesis in keloid tissue is greater than in normal skin and normal scar tissue. Inhibition of transforming growth factor beta (TGF-b) may control keloids and hypertrophic scars.

Currently, the treatment of keloid and hypertrophic scars is not consistently effective. Intralesional injection of a long-lasting synthetic glucocorticoid may make the lesion softer and smaller. Radiation therapy is ineffective and has the potential hazard of the development of skin cancer.

Marjolin's Ulcer This is a squamous carcinoma in a nonhealing wound. It appears to arise from dense scar tissue of the lesion that undergoes malignant transformation.

Tendon

Tendons are mainly composed of Type I collagen, with a significant amount of proteoglycan. The central component in the healing of a tendon within a fibrous flexor sheath is the segmental blood supply to the tendon through the vincula. Early motion provides stress forces to lengthen and remodel the scar. There is no evidence to suggest that the healing of tendons can be enhanced.

Bone

The healing process begins with inflammation and formation of a hematoma. There is a transformation of the surrounding osteoprogenitor cells and migration of hematogenous cells into the fracture site. This provides the fracture with platelets, monocytes, neutrophils, fibroblasts, osteoblasts, and osteoclasts—all needed to accomplish fracture repair.

Over the course of several weeks, there is the formation of a soft callus, a local fibrocartilaginous splint of granulation tissue. This gives the fracture some stability. In 6–8 weeks, the soft callus is transformed into bone by endochondral ossification. When rigid internal fixation is used to immobilize the injury, no soft callus forms, but instead there is direct bone-to-bone healing across the injury without endochondral ossification.

Delayed union or nonunion is a failure of fracture repair. The factors indicated are usually accompanying soft tissue injury, extensive bone loss, inadequate reduction, inadequate immobilization, infection, poor blood supply to the fracture, and malignant growth at the fracture site.

When nonunion occurs, bone grafts can be used to treat the established nonunion. Osteogenesis and osteoconduction are the primary mechanisms by which bone grafts heal. This occurs primarily in vascularized bone grafts, such as fibula flaps, in which the blood supply to the graft is maintained or reconstituted with a microvascular anastomosis. Osteoconduction is the process by which blood vessels and cells from the surrounding tissues grow into the bone graft and act as a scaffold for laying down new bone as the dead bone is resorbed.

Cartilage

Cartilage has little propensity to heal. Superficial injuries cause minimal inflammatory response, and healing depends on the chondrocytes' activity. The chondrocyte response is usually inadequate, and a persistent structural defect in the joint surface usually remains.

Cartilage grafts are used in reconstructive and cosmetic surgery. They maintain their structure with minimal resorption over time.

Chronic Wounds

Acute versus Chronic Wounds A chronic wound is one that fails to heal because of some underlying pathologic condition such as pressure, diabetes, and venous stasis. With proper clinical management, most chronic wound-healing problems can be resolved.

Pathophysiology Chronic wounds arise from physical and biochemical insults of extended duration. This prolongs the inflammatory stage of wound repair and results in extensive tissue damage and impaired healing. During normal wound repair, polymorphonuclear leukocytes (PNSs) quickly respond to chemoattractants, and infiltration lasts only a few days. With the preservation of damaged or necrotic tissue, there is an excessive response by the activated PNSs, and this continues to degrade the extracellular matrix and prevent the migration of other repairative cells into the wound.

Venous Stasis Ulcers These are the result of deep venous obstruction or valvular incompetence. The resulting increase in venous pressure promotes extravasation of fluid and high-molecular-weight proteins. Ulcers typically occur superior to or near the medial malleolus and are commonly rimmed by an area of hyperproliferative keratinocytes. The extent of the ulceration can range from just below the epidermis to the fascia.

Pressure Ulcers These occur over bony prominences. Immobilized persons are at particular risk. The pressure causes cell death in the least vascularized tissues. Patients with spinal cord injury are more susceptible to pressure ulcers because they do not have a normal leukocyte response to injury below the level of denervation.

The management of pressure ulcers requires good wound care. Antibiotics should not be used unless there is systemic toxicity.

Diabetic Ulcers Chronic ulcers in diabetics typically present as foot ulcers. Pressure and tissue trauma are major promoting factors, but the neuropathy from the primary disease is the most important element. The lack of sensation results in increased mechanical stress under the metatarsal heads, heels, and callosities. This leads to intermittent or continuous ischemia, resulting in pressure ulceration. Diabetics are also prone to angiopathy that interferes with the healing response.

Mechanisms Involved in the Healing of Chronic Ulcers Contraction can be involved by reducing the area of the wound. Usually minimal epithelialization is required to heal chronic ulcers. Venous ulcers heal mainly by epithelialization.

Chronic Wound Care

Most chronic wounds will heal by secondary intention only if the underlying biochemical and mechanical causative factors are corrected. Compression stockings or dressings must be used to relieve venous hypertension in the case of venous stasis ulcers. Pressure must be eliminated over pressure sores. The diabetes of a diabetic patient must be controlled to ensure healing of the ulcer. Bacterial counts above 100,000/g of tissue must be reduced and nutritional deficiencies corrected. An immunocompromised patient may require systemic or topical antibiotics to prevent or control infection. Low albumin levels should be corrected.

Tissue perfusion and cellular oxygenation are important factors for chronic wound repair. There is no evidence that hyperbaric oxygen can improve the healing of most chronic wounds with the exception of osteoradionecrosis.

Wound cleansing has a limited role. The objective of wound cleansing is not sterilization but rather reduction of the microbial load. Debridement to remove damaged and necrotic tissue often helps to accelerate healing. Sharp surgical debridement is the most effective method. Whirlpool treatment has been recommended for debridement of large areas, but care must be taken when this modality is used.

WOUND DRESSINGS

A wide variety of wound dressings are available. The classification, composition, indications, and functions of dressings are summarized in Table 8-2.

TABLE 8-2 WOUND DRESSINGS

MECHANICAL WOUND CLOSURE

Sutures are classified as absorbable or nonabsorbable. The nonabsorbable polypropylene suture is smooth and is advantageous when creating a subcuticular pullout suture. The absorbable polyglycolic dermal suture (PDS) is best for areas where long-term tensile strength is required. Both absorbable and nonabsorbable sutures can be used in most situations.

In addition to sutures, surgical staplers can be used to affect closures of intestines and skin. Tape strips are also helpful in supporting the wound margins. They allow early removal of skin sutures and also can be used to effect closure by themselves. Fibrin glue, a recent development, also has been applied to a variety of wounds.

FETAL WOUND HEALING

Fetal wound repair is characterized by a reduced inflammatory response. Fetal platelets have different aggregative characteristics and reduced cytokine release compared with adult platelets. Rather than collagen, the major component of the wound matrix is the glycosaminoglycan hyaluronic acid. There is a rapid turnover, remodeling, and reorganization of collagen during fetal repair. Amniotic fluid may inhibit fetal wound contraction.

For a more detailed discussion, see Cohen KI, Diegelmann RF, Yager DR, Wornum IL III, Graham M, and Crossland MC: Wound Care and Wound Healing, chap. 8 in Principles of Surgery, 7th ed.